GENE EXPRESSION IN HUMAN COLON CANCER

Project: Research project

Project Details

Description

We have developed unique methodology which permits quantitation of
expression of each of many thousands of cDNA sequences in small
biopsies taken from the human colonic mucosa. We have used this
method to identify 8 sequences, one of which is subunit 3 of
mitochondrial cytochrome c oxidase, whose level of expression
changes in progression from normal mucosa to benign adenoma and on
to colon carcinoma and whose expression is returned to the level
characteristic of the normal mucosa when colon carcinoma cells are
induced to differentiate in vitro. In addition, we have determined
that high risk polyposis mucosa involves changes in expression of
a far greater number of sequences. 29 clones were identified each
of whose level of expression provides good discrimination between
genetically high risk familial polyposis mucosa and genetically ow
risk mucosa.

Detection of risk has important practical implications for early
detection and prevention. In addition, genetic and other
predisposing risk for colon cancer may be more important in the
development of colon cancer in the general population than
previously appreciated. However, the mucosa at risk is essentially
indistinguishable from normal mucosa. We therefore propose to
study normal appearing mucosa from three genetic population groups
identified epidemiologically as at risk for colorectal cancer
(familial colon cancer families, heriditary non-polypotic colon
cancer, and Utah pedigrees) and quiescent flat mucosa from patients
with ulcerative colitis of >10 years duration. We will use the
methodology we have developed and the clones identified, as well
as analysis of expression of the genes for EGF, the EGFr, TGFa and
the laminin receptor to identify a panel of sequences which can
distinguish between genetically low risk flat mucosa and high risk,
and amongst the high risk groups. Specific sequences will be
selected from expression vector libraries we have made, analyzed
further, and antisera developed to the encoded protein to study the
changes in expression at the cellular level in biopsy tissue.
StatusFinished
Effective start/end date12/31/896/30/92

ASJC

  • Genetics
  • Molecular Biology
  • Oncology
  • Cancer Research

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